Trypanosoma cruzi-infected macrophages are defective in major histocompatibility complex class II antigen presentation.
Trypanosoma cruzi, the intracellular protozoan parasite that causes Chagas' disease, interferes with the host immune response to establish a persistent infection. In this report, we demonstrate that macrophages infected with T. cruzi are unable to effectively present antigens to CD4 T cells. The interference is due to defective antigen-presenting cell (APC) function, as antigen-independent stimulation of the T cell in the presence of infected macrophages is not affected. The defect is distal to antigen processing and is not due to decreased major histocompatibility complex (MHC) class II expression, decreased viability, defective peptide loading in the infected macrophages, nor absence of CD28 co-stimulation. There was a role for gp39: CD40 co-stimulation during antigen presentation to the T cells we studied, but the expression of CD40 on T. cruzi-infected macrophages was not decreased. Antigen-specific adhesion between macrophages and T cells was reduced by infection. Equivalent levels of the adhesion molecules lymphocyte function-associated antigen-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 or very late antigen-4 are found on infected and uninfected APC, suggesting that reduced expression of these adhesion molecules was not responsible for the defect in antigen-specific adhesion. The defective T cell:macrophage adhesion may be due to the reduced expression of other adhesion molecules or other changes in the cell induced by infection. Interfering with MHC class II antigen presentation in infected macrophages may help T. cruzi to blunt the immune response by the host.
La Flamme
A C
AC
Department of Pathobiology, University of Washington, Seattle 98195-7185, USA.
Kahn
S J
SJ
Rudensky
A Y
AY
Van Voorhis
W C
WC
D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology*; D000949:Histocompatibility Antigens Class II; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D014349:Trypanosoma cruzi / Q000276:immunology*
D000953:Antigens, Protozoan; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II